CLINICAL VIROLOGY FOURTH EDITION CLINICAL VIROLOGY FOURTH EDITION Douglas D. Richman Departments of Pathology and Medicine, University of California, San Diego School of Medicine, La Jolla, California, and Veterans Affairs San Diego Healthcare System, San Diego, California Richard J. Whitley DivisionofInfectiousDiseases,DepartmentsofPediatrics,SchoolofMedicine, University of Alabama at Birmingham, Birmingham, Alabama Frederick G. Hayden Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia Washington, DC Copyrightª2017byASMPress.ASMPressisaregisteredtrademarkoftheAmericanSocietyforMicrobiology.Allrightsreserved. Nopartofthispublicationmaybereproducedortransmittedinwholeorinpartorreutilizedinanyformorbyanymeans,electronic or mechanical, including photocopying and recording, or by any information storage and retrieval system, without permission in writingfromthepublisher. 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Description:Fourthedition.|Washington,DC:ASMPress,[2017] Identifiers:LCCN2016020817|ISBN9781555819422(hardcover)|ISBN9781555819439(e-ISBN) Subjects:LCSH:Virusdiseases.|Diagnosticvirology. Classification:LCCRC114.5.C562017|DDC616.9/1—dc23LCrecordavailableathttps://lccn.loc.gov/2016020817 AllRightsReserved PrintedinCanada 10 9 8 7 6 5 4 3 2 1 Addresseditorialcorrespondenceto:ASMPress,1752NSt.,N.W.,Washington,DC20036-2904,USA. Sendordersto:ASMPress,P.O.Box605,Herndon,VA20172,USA. Phone:800-546-2416;703-661-1593.Fax:703-661-1501. E-mail:[email protected] Online:http://www.asmscience.org DEDICATION To our families—Eva, Sara, Matthew andIsabella; Kevin, Sarah, Christopher, Jennifer, and Katherine; Melissa, Dan, Gabi, Gretta, Grant, Geoff, Mary, Cotes, andAnderson—and toour many colleagues and friends, who have inspired andsupported us throughout the years. Contents Contributors 11.Antiretroviral Agents / 169 CHRISTINEJ.KUBIN,BARBARAS.TAYLOR, ConflictsofInterest ANDSCOTTM.HAMMER Preface 12.Antiherpesvirus Agents / 215 CLAIREL.GORDON,CHRISTINEJ.KUBIN, ImportantNotice(PleaseRead) ANDSCOTTM.HAMMER 1. Introduction / 1 13.Anti–Hepatitis Virus Agents / 239 DOUGLASD.RICHMAN,RICHARDJ.WHITLEY, MATTHEWL.SCHERER,CHELSEASAMMONS, ANDFREDERICKG.HAYDEN BRIANNELSON,SCOTTM.HAMMER, ANDELIZABETHVERNA I 14.AntirespiratoryVirus Agents / 271 MARCUSR.PEREIRA,BENJAMINA.MIKO, Section MONICAMEHTA,ANDSCOTTM.HAMMER 15.Diagnosis of Viral Infections / 291 Viral Syndromes and GUYBOIVIN,TONYMAZZULLI, General Principles ANDMARTINPETRIC 16.Immune Responses to Viral Infection / 321 HENDRIKSTREECK,TODDJ.SUSCOVICH, 2. RespiratoryInfections / 9 ANDGALITALTER JOHNJ.TREANOR 17.Immunization Against Viral Diseases / 351 3. Viral Infections of the Central Nervous JULIEE.LEDGERWOOD System / 31 ANDBARNEYS.GRAHAM KEVINA.CASSADYANDRICHARDJ.WHITLEY 18.Chronic Fatigue and Postinfective Fatigue 4. Gastrointestinal Syndromes / 47 Syndromes / 371 EYALLESHEMANDUMESHD.PARASHAR ANDREWR.LLOYD 5. Viral Hepatitis / 61 ZINAS.VALAYDON,STEPHENA.LOCARNINI, ANDALEXANDERJ.V.THOMPSON II 6. Viral Infections in Organ Transplant Recipients / 75 Section JOHNA.ZAIA The Agents 7. Viral Heart Disease / 99 BRUCEM.McMANUS,MICHAELSEIDMAN, Part A: DNA Viruses KARINKLINGEL,ANDHONGLINLUO 8. Viral Diseases of the Skin / 115 19.Poxviruses / 387 ZEENAY.NAWASANDSTEPHENK.TYRING STUARTN.ISAACSANDR.MARKBULLER 9. Viral Hemorrhagic Fevers / 141 20.Herpes Simplex Viruses / 415 GAILCARSON,MIKEBRAY,ANDCATHYROTH RICHARDJ.WHITLEYANDBERNARDROIZMAN 10.Viral Disease of the Eye / 151 21.Cercopithecine Herpesvirus 1 (B Virus) / 447 HOWARDM.NEWMAN RICHARDJ.WHITLEY vii viii - CONTENTS 22.Varicella-Zoster Virus / 459 40.Zoonotic Paramyxoviruses / 949 ANNEA.GERSHONANDMICHAELD.GERSHON DANIELLEE.ANDERSONANDLIN-FAWANG 23.Cytomegalovirus / 481 41.Rhabdoviruses / 967 PAULDAVIDGRIFFITHSANDMATTHEWREEVES ALANC.JACKSON 24.Human Herpesvirus 6 and Human 42.Filoviruses / 981 Herpesvirus 7 / 511 MIKEBRAYANDDANIELS.CHERTOW KOICHIYAMANISHIANDYASUKOMORI 43.Influenza Virus / 1009 25.Epstein-Barr Virus / 523 FREDERICKG.HAYDENANDPETERPALESE JOYCEFINGEROTH 44.Bunyaviridae: Orthobunyaviruses, 26.Kaposi’s Sarcoma-Associated Herpesvirus Phleboviruses, Nairoviruses, (KSHV/HHV8) / 549 and Hantaviruses / 1059 YUANCHANG,SHOU-JIANGGAO, GREGORYJ.MERTZ,CLASAHLM, ANDPATRICKS.MOORE ANDCOLLEENB.JONSSON 27.Adenoviruses / 575 45.Arenaviruses / 1089 OLLIRUUSKANEN,JORDANP.METCALF, DANIELG.BAUSCH MATTIWARIS,ANDGÖRANAKUSJÄRVI 46.Enteroviruses / 1113 28.Polyomaviruses / 599 JOSÉR.ROMERO JOHNE.GREENLEEANDHANSH.HIRSCH 47.Rhinovirus / 1143 29.Papillomavirus / 625 WAI-MINGLEEANDJAMESE.GERN WILLIAMBONNEZ 48.Hepatitis A Virus / 1165 30.Human Parvoviruses / 679 SARAE.WILLIFORDANDSTANLEYM.LEMON MARIASÖDERLUND-VENERMO, 49.Human Caliciviruses / 1189 KEVINE.BROWN,ANDDEAND.ERDMAN ROBERTL.ATMARANDMARYK.ESTES 31.Anelloviridae / 701 50.Hepatitis EVirus / 1209 PETERSIMMONDSANDCOLINP.SHARP HARRYR.DALTON,NASSIMKAMAR, 32.Hepatitis B Virus / 713 ANDJACQUESIZOPET DARRENJ.WONG,STEPHENA.LOCARNINI, 51.Astrovirus / 1231 ANDALEXANDERJ.V.THOMPSON CARLOSF.ARIASANDTOMÁSLÓPEZ 52.Coronaviruses / 1243 Part B: RNA Viruses J.S.M.PEIRIS 53.Arthropod-BorneFlaviviruses / 1267 33.Human Lymphotropic Viruses: HTLV-1 LYLER.PETERSENANDALAND.T.BARRETT and HTLV-2 / 771 54.Hepatitis C Virus / 1313 ROBERTAL.BRUHN,RENAUDMAHIEUX, CHRISTOPHERKOH,QISHENGLI, ANDEDWARDL.MURPHY ANDJAKELIANG 34.Human Immunodeficiency Virus / 795 55.Alphaviruses / 1347 JOHNC.GUATELLI,ROBERTF.SILICIANO, DAVIDW.SMITH,JOHNS.MACKENZIE, DANIELR.KURITZKES,AND ILYAV.FROLOV,ANDSCOTTC.WEAVER DOUGLASD.RICHMAN 56.RubellaVirus / 1381 35.Colorado Tick Fever and Other Arthropod DAVIDW.KIMBERLIN Borne Reoviridae / 841 STEVENYUKLANDJOSEPHK.WONG 57.Infections Caused by Bornaviruses / 1395 RALFDÜRRWALD,NORBERTNOWOTNY, 36.Rotaviruses / 853 MARTINBEER,ANDJENSH.KUHN MANUELA.FRANCO,JUANAANGEL, ANDHARRYB.GREENBERG Part C: Subviral Agents 37.RespiratorySyncytial Virus, Human Metapneumovirus, andParainfluenza 58.Hepatitis D / 1409 Viruses / 873 MARIORIZZETTO,ANTONINASMEDILE, JOHNV.WILLIAMS,PEDROA.PIEDRA, ANDALESSIACIANCIO ANDJANETA.ENGLUND 59.Prion Diseases / 1425 38.Measles / 903 CHRISTINAJ.SIGURDSON,MEE-OHKKIM, WILLIAMJ.MOSSANDDIANEE.GRIFFIN ANDMICHAELD.GESCHWIND 39.Mumps Virus / 929 JOHNW.GNANN,JR.ANDDONALDR.LATNER SubjectIndex / 1449 Contributors CLAS AHLM GUY BOIVIN UmeåUniversity,DepartmentofClinicalMicrobiology CHUdeQuébec-LavalUniversity S-90187Umeå,Sweden QuebecCity,QC,CanadaG1V4G2 GÖRAN AKUSJÄRVI WILLIAM BONNEZ UppsalaUniversity UniversityofRochesterSchoolofMedicineandDentistry Uppsala75123Sweden Rochester,NY21702 GALITALTER MIKE BRAY RagonInstituteforMGH,MITandHarvard NationalInstitutesofHealth Cambridge,MA02139 Bethesda,MD20892 DANIELLEE. ANDERSON KEVIN E.BROWN ProgrammeinEmergingInfectiousDiseases PublicHealthEngland,VirusReferenceDepartment Duke-NUSMedicalSchool, London,NW95EQ,UnitedKingdom 8CollegeRoad Singapore169857 ROBERTA L.BRUHN JUANA ANGEL BloodSystemsResearchInstitute FacultaddeMedicina,InstitutodeGenéticaHumana SanFrancisco,CA94118 PontificiaUniversidadJaveriana Bogotá,Colombia R.MARK BULLER SaintLouisUniversitySchoolofMedicine CARLOSF. ARIAS St.Louis,MO63104 InstitutodeBiotecnología/UNAM Cuernavaca62210,Mexico GAIL CARSON NuffieldDepartmentofMedicine ROBERTL. ATMAR UniversityofOxford BaylorCollegeofMedicine Oxford,UnitedKingdom Houston,TX77030 KEVIN A. CASSADY ALAN D.T. BARRETT NationwideChildren’sHospital UniversityofTexasMedicalBranch Columbus,OH43205 Galveston,TX77555 DANIEL G. BAUSCH YUAN CHANG TulaneSchoolofPublicHealthandTropicalMedicine UniversityofPittsburghCancerInstitute NewOrleans,LA70112 Pittsburgh,PA15213 MARTIN BEER DANIEL S. CHERTOW Friedrich-Loeffler-Institut NationalInstitutesofHealth Greifswald—InselRiems17493,Germany Bethesda,MD20892 ix